Process for the preparation of methylaluminium dichloride

ABSTRACT

A process of preparing methylaluminium dichloride by  
     (i) reacting by heating a material of the formula R 3 Al 2 X 3 , where R is C 1 -C 4  alkyl and X is selected from bromine and iodine with an aluminium-containing material selected from metallic aluminium and a mixture of metallic aluminium and aluminium trichloride in an atmosphere of methyl chloride, with the proviso that when R is methyl and X is iodine, the aluminium-containing material is a mixture of aluminium and aluminium trichloride; and (ii) when the aluminium-containing material is metallic aluminium, adding aluminium trichloride to this reaction mixture and heating, to give a crude reaction product; and (iii) if desired, obtaining methylaluminium dichloride from this crude reaction product. The crude reaction product may be used directly in organic syntheses, such as the cyclisation of ψ-Georgywood to give β-Georgywood.

This invention relates to a method of preparing methylaluminiumdichloride and to its use in the preparation of certain fragrantsubstances.

Methylaluminium dichloride (MADC) was characterised and procedures forits preparation were published some time ago (for example, J. Org. Chem.5, 106 (1940)). Several later publications described its preparation(for example, J. Am. Chem. Soc. 73, 2854 (1951) and U.S. Pat. No.2,712,546).

MADC is potentially useful as a Lewis acid in syntheses, but its use hasbeen hindered by the fact that is is difficult to make consistently andinexpensively on an industrial scale (see, for example, Houben-Weyl“Methoden der organischen Chemie” (Thieme Verlag, 1970), Bd 13/4, pp.59-78).

It has now been found that it is possible to prepare MADC by a cheap,efficient process that gives a good yield of the compound. It has theadditional advantage that the unpurified compound as prepared can beused directly in the preparation of desirable organic compounds. Theinvention therefore provides a process for the preparation of MADCcomprising the steps of

(i) reacting by heating a material of the formula R₃Al₂X₃, where R isC₁-C₄ alkyl and X is selected from bromine and iodine, with analuminium-containing material selected from metallic aluminium and amixture of metallic aluminium and aluminium trichloride in an atmosphereof methyl chloride, with the proviso that, when R is methyl and X isiodine, the aluminium-containing material is a mixture of aluminium andaluminium trichloride; and

(ii) when the aluminium-containing material is metallic aluminium,adding aluminium trichloride to this reaction mixture and heating, togive a crude reaction product; and

(iii) if desired, obtaining methylaluminium dichloride from this crudereaction product.

The compound of formula R₃Al₂X₃ as hereinabove defined (hereinafter “thesesquihalide”) may be any such material, but it is preferably selectedfrom methylaluminium sesquiiodide (MASI) and ethylaluminiumsesquibromide (EASB). The sesquihalide may be a pure material, but it ispreferably the crude mixture of unreacted raw materials and productresulting from the preparation method described by Grosse and Mativy inJ. Org. Chem. 5, 106 (1940), the details of which are incorporatedherein by reference. This describes the MASI preparation, (in this case,the mixture is aluminium, unreacted methyl iodide and MASI), but EASBand the other sesquihalides may be prepared by an exactly analogousmethod.

This crude sesquihalide mixture is added directly to analuminium-containing material. The aluminium-containing material ispreferably metallic aluminium in particulate form, more preferably it isaluminium gritty. An example of a suitable material is Fluka™ 11008 inthe Sigma-Aldrich Catalogue. The aluminium-containing material may alsobe a mixture of metallic aluminium and aluminium trichloride. When thesesquihalide is MASI, the aluminium-containing material must be such amixture. The weight ratio of Al to AlCl₃ is preferably from 2:1 to 3:1.

The method comprises the following steps:

(i) the crude sesquihalide mixture is sprinkled over thealuminium-containing material in an atmosphere of methyl chloride at apressure of 1 bar, and the mixture heated; and then

(ii) when the aluminium-containing material is metallic aluminium, thealuminium chloride is added and the mixture is again heated.

Naturally, when the aluminium-containing compound is analuminium/aluminium trichloride mixture, step (ii) above is unnecessary.

The following reaction conditions are typical and are given by way ofguidance only—the skilled person will know what adjustments will benecessary in each case. Although they are described with reference tothe preferred MASI and EASB, the same principles apply for thepreparation of all sesquihalides.

The reaction conditions needed to start the reaction are slightlydifferent, depending on whether MASI or EASB will be used. The startingtemperature for MASI may be room temperature (20-25° C.), but slightheating may be needed in the case of EASB (about 45° C.). From thispoint on, the conditions are similar; the temperature is raised to about115°-120° C. and maintained there for 4-6 h. At this point, thetemperature is lowered to 60°-70° C., and non-polar solvent, typicallytoluene or cyclohexane, may be added, if need be.

The yield in both cases is typically at least 75% MADC, based on theweight of the aluminium-containing material.

The proportions of crude sesquihalide used are from 0.2-20%, preferablyfrom 0.5-5% by weight of the aluminium-containing material. Withoutrestricting the invention in any way, it is believed that thesesquihalide acts as an activator for the aluminium. It is preferred notto exceed 10% purely for cost reasons—more can be used, but it has nogreater effect.

If desired, pure MADC may be produced from the resulting crude MADC bydistillation. However, in another aspect of this invention, this crudeMADC may be used in this form to promote a desirable organic reaction.Thus, the invention also provides a method of producing β-Georgywood,comprising the addition of pseudo-Georgywood (ψ-Georgywood) to theabovementioned crude MADC.

β-Georgywood(cis-2-acetyl-1,2,3,4,5,6,7,8-octahydro-1,2,8,8-tetramethylnaphthalene)is a fragrance ingredient having the formula I:

This fragrant material is described in U.S. Pat. No. 5,707,961, thedetails of which are incorporated herein by reference. It is known fromthis patent that Compound I may be prepared by the cyclisation ofψ-Georgywood(cis-1-[1,2-dimethyl-4(4-methyl-pent-3-enyl)-cyclohex-3-enyl]-ethanone—FormulaII):

The method of preparing the compound of Formula I from that of FormulaII is described in paragraph (d) of Example 1 of the abovementioned USpatent. However, that preparation gives a mixture of Compound I and itsstructural isomer iso-Georgywood, shown in Formula III:

The compound of Formula I has particularly desirable olfactoryproperties. It is therefore desirable to increase the proportion of thecompound of Formula I in the mixture. Achieving this using thetechnology of U.S. Pat. No. 5,707,961 is very difficult.

The process of preparation of β-Georgywood according to the presentinvention gives a number of distinct advantages:

1. The compound of Formula I is obtained in a yield of more than 80% andin a purity of higher than 90%. The compound of Formula III is presentonly in trace amounts (less than 1%).

2. The reaction can be carried out as a “one pot” reaction, that is, allthe reactions from the initial MADC preparation to the final productreaction can be carried out in a single reaction vessel, without theneed to isolate and purify intermediates.

Both of these are of considerable significance to the preparation ofβ-Georgywood on a commercial scale.

A further advantage of the method of this invention is that the compoundof Formula I made by the abovementioned process can be easilydecoloured, something that is difficult to achieve with productsobtained from iodine-containing reagents. For example, a productobtained using MASI as starting material is easily decoloured bystirring or distilling over an acidic clay. In this regard, the productobtained by using EASB as starting material is even better, in thatdecolorisation is not necessary.

The process is carried out simply by adding Compound II to the crudeMADC and heating for about 4 hours at about 60°-70° C.

The invention is further described with reference to the followingnon-limiting examples.

EXAMPLE 1 Preparation of Crude MASI, Crude MASC and MADC (Distilled)

Under nitrogen 18.2 g (0.13 mol) methyl iodide and 2 g (0.75 mol)aluminium gritty (Fluka™ 110008) are heated to reflux (45° C.) for 8-12h. The resulting crude MASI reaction mixture can be stored undernitrogen for several weeks without loss of activity.

16.2 g (0.6 mol) aluminium gritty (Fluka 11008) is placed under 1 atm ofmethyl chloride (dried over a column filled with KOH) in a sulphonationflask equipped with a reflux condenser and a balloon fixed on thegas-outlet. 0.4 ml (ca. 5% w/w) of the above aluminium/methyliodide/MASI mixture is sprinlded via syringe over the aluminium at 90°C. The reaction starts with a temperature rise to 120° C. and formationof liquid MASC. Under stirring, the reaction temperature is maintainedat 120° C. for 4 h (by means of slight cooling and regulation of themethyl chloride flow) until the exothermy and the methyl chloride uptake(56 g, 1.1 mol) cease and the theoretical volume of 54 ml (d=1.15)liquid MASC is reached.

The methyl chloride atmosphere is replaced by nitrogen. The black liquidis cooled to 60° C., at which point 29 g (0.22 mol) aluminium chlorideis added via a nitrogen-flushed proportioning screw. The blacksuspension is heated to 120° C. and maintained there for 30 min.Formation of MADC can be checked by briefly cooling to under 55° C., atwhich temperature the reaction mass solidifies. The proportioning screwis replaced by a distillation bridge and the MADC is distilled under 1atm of nitrogen at bpt.=157° C. to give 69.3 g (75% based on aluminiumand aluminium trichloride) of colourless MADC, which crystallizes atroom temperature in long white needles.

Analytical Data:

MASI (crude): ²⁷Al-NMR (neat): 71 (W_(1/2)=14800 Hz) ppm.

MASC (crude): ²⁷Al-NMR (hexane): 177 (W_(1/2)=7600 Hz), 136(W_(1/2)=6000 Hz) ppm.

MADC (dist): Fp=73° C., bp=157° C. ²⁷Al-NMR (hexane): 136 (W_(1/2)=6000Hz) ppm.

EXAMPLE 2 Cyclization of Pseudo-Georgywood (ψ-Georgywood) WithCommercial MADC:(cis-2-acetyl-1,2,3,4,5,6,7,8-octahydro-1,2,8,8-tetramethylnaphthalene(β-Georgywood)

20 g (85 mmol) ψ-Georgywood dissolved in 100 g toluene is added underice cooling to 157 g (0.21 mol) MADC (1 M in hexane, Aldrich™ 29680-5).The mixture is heated to 70° C. for 2-3 h, then quenched underice-cooling with 40 g ethanol, then with 2M HCl. The organic phase isseparated and the aqueous phase extracted with t-butyl methyl ether. Thecombined organic layers are washed with conc. NaCl, then with wateruntil pH=7. The organic phase is dried over MgSO₄, filtered andconcentrated under reduced pressure. The residue is distilled over ashort Vigreux column (124° C./0.1 Torr) to give 16 g (80%) ofβ-Georgywood as a colorless liquid (GC purity˜90%).

Analytical Data:

IR (film): 2930 m, 1700 s (C═O), 1560 m, 1377 m, 1357 m, 1240 w, 1220 w,1090 m.

GC/MS: 234 (25%, [M]⁺), 219 (15%, [M—CH₃]⁺), 191 (100%, [M—Ac]⁺, 161(20%), 135 (65%), 121 (40%), 105 (40%), 91 (30%), 69 (30%), 43 (55%).

¹H-NMR (CDCl₃, 400 MHz): 0.85 (d, 3H, J=6.9 Hz, Cl—Me), 0.99 (s, 3H),1.02 (s, 3H), 1.06 (s, 3H), 1.4-2.2 (10 H, 5 CH₂), 2.15 (s, 3H, Ac—Me),2.36 (q, 1H, J=6.9 Hz, Cl-H) ppm.

¹³C-NMR (CDCl₃, 400 MHz): 19.1 (CH₂), 19.7 (CH₃), 21.0 (CH₃), 22.5(CH₂), 24.9 (CH₃), 27.7 (CH₂), 28.9 (CH₃), 29.4 (CH₃), 30.8 (CH₂), 34.0(C), 35.4 (CH), 40.1 (CH₂), 50.7 (C), 125.9 (C═), 136.9 (C═), 214.5(C═O) ppm.

EXAMPLE 3 Cyclization of Pseudo-Georgywood With Crude MADC via MASIActivation of Aluminium in the Presence of AlCl₃: β-Georgywood

1.5 ml (ca. 0.013 mol) of the aluminium/methyl iodide/MASI mixtureprepared according to example 1 is sprinkled via syringe onto a stirredmixture of 42.9 g (1.59 mol) of aluminium gritty (Fluka™ 11008) and105.0 g (0.79 mol) of aluminium trichloride flakes (Fluka 06220) under 1atm of methyl chloride at room temperature. The reaction starts almostat once and the initially solid reaction mixture progressively turnsinto a liquid. The methyl chloride absorption rate is kept approximatelyconstant by gradually increasing the temperature from 25 to 120° C. overthe next 2 h. The reaction is then allowed to proceed at 120° C. untilno more gas absorption is observed (about 1 h). This happens after about156.0 g (3.09 mol) of methyl chloride has been consumed. The crudemolten MADC is cooled down to 70° C., the methyl chloride atmosphere isexchanged for an argon one and 810 g of dry toluene is added.

The ca. 25 wt % suspension of crude MADC in toluene thus obtained iscooled to 10-15° C. and 275.0 g (1.06 mol) of 90% pure pseudo-Georgywoodis added dropwise. The mixture is heated at 70° C. until nearly completecyclization of pseudo-Georgywood is detected by GC (about 2-3 h). Thereaction mixture is cooled to 0° C. and pumped via a double-tippedneedle on to 1.8 kg of ice-cooled 5% aqueous hydrochloric acid. Theorganic layer is separated, washed until neutral and refluxed for 2 hover 30.0 g of Montmorillonite K10, an acidic clay. Filtration andconcentration of the organic layer under reduced pressure gives crudeβ-Georgywood, which is rectified over 3 weight % of Montmorillonite K10through a 2.5×20 cm Vigreux column (105-110° C./1 mbar) to give 227 g(82.5% based on pseudo-Georgywood) β-Georgywood (GC-purity 86%) of ayellow colour.

Two further distillations over 10 weight % of paraffin oil and 3 weight% of Montmorillonite K10 give nearly colorless β-Georgywood.

Analytical data: Identical with those from Example 2

Example 4 Cyclization of Pseudo-Georgywood With Crude MADC via EASBActivation of Aluminium in the Presence of AlCl₃: β-Georgywood

10.0 g (0.37 mol) of aluminium gritty (Fluka™ 11008) suspended in 87.7 g(0.81 mol) of ethyl bromide is refluxed for 18 hours at 40°-65° C. undernitrogen atmosphere. The crude EASB reaction mixture thus obtained canbe stored under nitrogen atmosphere for several weeks without any lossof activity.

A stirred mixture containing 47.1 g (1.75 mol) of aluminium gritty(Fluka 11008) and 115.5 g (0.87 mol) of aluminium trichloride flakes(Fluka 06220) is heated for 30 minutes at 40-45° C. under 1 atm ofmethyl chloride. At this temperature, 9 ml (ca. 0.05 mol) of theabove-prepared crude aluminium/ethyl bromide/EASB mixture is sprinkledvia syringe on to the contents of the vessel and the reaction startsalmost at once. The methyl chloride absorption rate is keptapproximately constant by gradually increasing the temperature from 45to 120° C. over the next 3 h and the initially solid reaction mixtureprogressively turns into a liquid. The reaction mixture is then heatedfor a further 3 h at 120° C., during which period of time gas absorptionstops after an average amount of 186.0 g (3.69 mol) of methyl chloridehas been consumed. The crude molten MADC is cooled to 70° C., the methylchloride atmosphere is exchanged for an argon one and 810 g of drytoluene is added.

The ca. 27 wt % suspension of crude MADC in toluene thus obtained iscooled to 10-15° C. and 275.0 g (1.06 mol) of 90% pure pseudo-Georgywoodis added dropwise. The mixture is heated to 70° C. until nearly completecyclization of pseudo-Georgywood is detected by GC (about 4 h). Thereaction mixture is cooled to 0° C. and pumped via a double-tippedneedle on to 1.8 kg of ice-cooled 5% aqueous hydrochloric acid. Theorganic layer is separated, washed until neutral and concentrated underreduced pressure to give crude β-Georgywood which is rectified through a2.5×31 cm Sulzer DX type column (105-110° C./1 mbar) to give 224.5 g(82%) β-Georgywood (GC purity 89%).

Analytical data: Identical with those from Example 2.

1. A process for the preparation of methylaluminium dichloridecomprising the steps of: (i) reacting, by heating a material of theformulaR₃Al₂X₃, where R is C₁-C₄ alkyl and X is selected from bromine andiodine with an aluminium-containing material selected from metallicaluminium and a mixture of metallic aluminium and aluminium trichloridein an atmosphere of methyl chloride, with the proviso that when R ismethyl and X is iodine, the aluminium-containing material is a mixtureof aluminium and aluminium trichloride; and (ii) when thealuminium-containing material is metallic aluminium, adding aluminiumtrichloride to this reaction mixture and heating, to give a crudereaction product; and (iii) optionally obtaining methylaluminiumdichloride from this crude reaction product.
 2. A process according toclaim 1, in which the material of the formula R₃Al₂X₃ is selected frommethylaluminium sesquiiodide and ethylaluminium sesquibromide.
 3. Aprocess according to claim 1 in which the material of the formulaR₃Al₂X₃ is a crude mixture of unreacted raw materials and productresulting from the preparation method described by Grosse and Mativy inJ. Org. Chem. 5, 106 (1940).
 4. A process according to claim 1, in whichthe metallic aluminium is particulate metallic aluminium.
 5. A processfor preparing a compound of the Formula I

comprising the addition of a compound of Formula II

to the crude reaction product of a reaction according to claim
 1. 6. Aprocess for the preparation of a compound of Formula I

by cyclisation of a compound of Formula II

of a reaction mixture according to the steps of: (i) reacting by heatinga material of the formulaR₃Al₂X₃, where R is C₁-C₄ alkyl and X is selected from bromine andiodine with an aluminium-containing material selected from metallicaluminium and a mixture of metallic aluminium and aluminium trichloridein an atmosphere of methyl chloride, with the proviso that when R ismethyl and X is iodine, the aluminium-containing material is a mixtureof aluminium and aluminium trichloride; and (ii) when thealuminium-containing material is metallic aluminium, adding aluminiumtrichloride to this reaction mixture and heating.